TY - JOUR
T1 - Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate with prednisone within step-up treatment strategies in early rheumatoid arthritis
T2 - an indirect comparison of effectiveness and safety of the U-Act-Early and CAMERA-II treat-to-target trials
AU - Verhoeven, Maxime M.A.
AU - De Hair, Marjolein J.H.
AU - Tekstra, Janneke
AU - Bijlsma, Johannes W.J.
AU - Van Laar, Jacob M.
AU - Pethoe-Schramm, Attila
AU - Borm, Michelle E.A.
AU - Ter Borg, Evert Jan
AU - Linn-Rasker, Suzanne P.
AU - Teitsma, Xavier M.
AU - Lafeber, Floris P.J.G.
AU - Jacobs, Johannes W.G.
AU - Welsing, Paco M.J.
N1 - Funding Information:
The U-Act-Early trial was funded by Roche Nederland BV, and the CAMERA-II trial was financially supported by the Catharijne Foundation (grant 20063).
Funding Information:
Funding The U-act-early trial was funded by Roche nederland BV, and the CaMeRa-ii trial was financially supported by the Catharijne Foundation (grant 20063).
Publisher Copyright:
© © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - OBJECTIVES: Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.METHODS: Using individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders.RESULTS: DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: -0.62 (95% CI -1.14 to -0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies.CONCLUSIONS: In patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.
AB - OBJECTIVES: Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.METHODS: Using individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders.RESULTS: DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: -0.62 (95% CI -1.14 to -0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies.CONCLUSIONS: In patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.
KW - early rheumatoid arthritis
KW - glucocorticoids
KW - methotrexate
KW - tocilizumab
KW - treat-to-target
UR - http://www.scopus.com/inward/record.url?scp=85067277691&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2019-215304
DO - 10.1136/annrheumdis-2019-215304
M3 - Article
C2 - 31196844
AN - SCOPUS:85067277691
SN - 0003-4967
VL - 78
SP - 1333
EP - 1338
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 10
ER -